The overall objective of the proposed research is to continue the use of the hamster estrogen induced and dependent renal carcinoma as a model to study estrogen carcinogenicity, tumor hormone dependency, and transition from estrogen dependency to autonomy. It is our aim to focus our research effort in two specific areas in which we believe there is an urgent need for information. First, we hope to elucidate the mechanism of estrogen carcinogenicity in the hamster kidney and the influence of other steroidal agents (i.e. androgens, progestins, antiestrogens, corticoids) on tumor induction and hopefully such knowledge would shed light on the etiology of estrogen associated human tumors. It is our goal to identify and localize estrogen metabolites in renal cellular constituents at varying intervals of tumor induction (latency period). Secondly, our demonstration that all of the major classes of steroid receptors are present in the hamster neoplasia provide a unique system to study both in-vivo and in-vitro the hormonal interrelationships involved in tumor response to endocrine therapy as well as the interaction of steroid hormones within a single tissue. A principal goal is to work out the basic biochemical actions of the antiestrogen, antiandrogen, and progestin group of drugs and selected antineoplastic agents, used alone or in combination, which prevent tumor induction and effect tumor regression in this system. The endpoint in these studies will be estrogen-induced progesterone receptor synthesis in the estrogenized kidney and labeled thymidine, uridine, and leucine incorporation in the tumor. These studies should lead to a greater understanding of the mechanisms by which steroids support or inhibit growth of dependent tumors thus facilitating more precise treatment of human breast, endometrial, and prostate cancer. We also intend to continue surveillance of steroid receptor binding in human renal cell cancer and prostatic cancer to determine the incidence of hormone dependence in an effort to improve treatment.